Memory Enhancement Using Transcranial Alternating Current Stimulation

Alzheimer Disease Clinical Trial

— Memento  

Official title:

Memory Enhancement Using Transcranial Alternating Current Stimulation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06202872
• Other study ID #: 20212222
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 1, 2024
• Est. completion date: February 1, 2026

Study information

• Verified date: January 2024
• Source: Amsterdam UMC, location VUmc
• Contact: Willem de Haan, dr.
• Phone: (0)20 444 0722
• Email: w.dehaan[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The 32 million Alzheimer's disease (AD) and 69 million prodromal AD patients worldwide contribute to a large economic burden. Effective and safe therapies that slow or prevent the progression from mild cognitive impairment (MCI) to AD are therefore of high priority. Transcranial alternating current stimulation (tACS) is a safe and patient-friendly non-invasive brain stimulation technique that serves as a potential candidate for reducing and/or slowing cognitive impairment. Application of tACS in the gamma frequency range, specifically around 40 Hz, has been studied in patients with AD and MCI due to AD. In these patients, a single session of 40 Hz tACS at the precuneus showed to improve episodic memory and to increase gamma power, as measured with electroencephalography. These findings will be replicated in the current study in patients with MCI due to AD, using magnetoencephalography (MEG) recorded before, during and after tACS. In this way, brain activity and network changes that underlie this improvement in episodic memory can be studied with greater temporal and spatial detail.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: February 1, 2026
• Est. primary completion date: February 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Recent (not more than 6 months ago) amnestic MCI diagnosis, which consensus is obtained in a multidisciplinary meeting after an extended multidisciplinary test battery at the memory clinic, including confirmation of AD pathology with cerebrospinal fluid biomarkers: abnormal p-tau/Aß42 ratio of > 0.023

Exclusion Criteria:

• Suffering from serious neurological, psychiatric or somatic comorbidity
• Suffering from epileptic seizures or severe claustrophobia
• Intensive use of psychoactive medication
• Having a cardiac pacemaker, internal cardiac defibrillator or other intracorporeal device that interferes with MEG recordings

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Device:
• Gamma (40 Hz) tACS at the precuneus region
40 Hz tACS applied at a current of 3 milliampere peak-to-peak using a NuroStym transcranial electrical stimulation (tES) system of NeuroDevice for four times 12 minutes (48 minutes in total) at the Pz (according to the 10-20 international EEG coordinates)
• Sham tACS at the precuneus region
Sham tACS applied with no effective stimulation between the ramp-up and ramp-down of the current using a NuroStym tES system of NeuroDevice for four times 12 minutes (48 minutes in total) at the Pz (according to the 10-20 international EEG coordinates)

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC, location VUmc	Amsterdam	Noord-Holland

Sponsors (1)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc

Country where clinical trial is conducted

Netherlands, 

References & Publications (6)

Benussi A, Cantoni V, Cotelli MS, Cotelli M, Brattini C, Datta A, Thomas C, Santarnecchi E, Pascual-Leone A, Borroni B. Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Brain Stimul. 2021 May-Jun;14(3):531-540. doi: 10.1016/j.brs.2021.03.007. Epub 2021 Mar 21. — View Citation

Benussi A, Cantoni V, Grassi M, Brechet L, Michel CM, Datta A, Thomas C, Gazzina S, Cotelli MS, Bianchi M, Premi E, Gadola Y, Cotelli M, Pengo M, Perrone F, Scolaro M, Archetti S, Solje E, Padovani A, Pascual-Leone A, Borroni B. Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease. Ann Neurol. 2022 Aug;92(2):322-334. doi: 10.1002/ana.26411. Epub 2022 Jun 6. — View Citation

Grover S, Fayzullina R, Bullard BM, Levina V, Reinhart RMG. A meta-analysis suggests that tACS improves cognition in healthy, aging, and psychiatric populations. Sci Transl Med. 2023 May 24;15(697):eabo2044. doi: 10.1126/scitranslmed.abo2044. Epub 2023 May 24. — View Citation

Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7;540(7632):230-235. doi: 10.1038/nature20587. Erratum In: Nature. 2018 Oct;562(7725):E1. — View Citation

Maestu F, de Haan W, Busche MA, DeFelipe J. Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology. Ageing Res Rev. 2021 Aug;69:101372. doi: 10.1016/j.arr.2021.101372. Epub 2021 May 21. — View Citation

Palop JJ, Mucke L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nat Rev Neurosci. 2016 Dec;17(12):777-792. doi: 10.1038/nrn.2016.141. Epub 2016 Nov 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Rey Auditory Verbal Learning test scores	The Rey Auditory Verbal Learning test evaluates verbal episodic memory and is designed as a list-learning paradigm in which the subject hears a list of 15 nouns. The participant is asked to recall as many words from the list as possible after each of 5 repetitions of free-recall (total recall), and 15 minutes after an interference trial (long delayed recall). Scores range from 0 to 15, with higher scores meaning a better outcome.	Immediately before and after intervention
Primary	Change in Face-Name Association Task scores	The Face-Name Association Task assesses associative episodic memory and is a computer paradigm consisting of an encoding and a retrieval phase of face-name pairs. During the encoding phase, participants are instructed to remember a set of faces and the names they are paired with. During the retrieval phase, 5 minutes after the encoding phase, participants are shown a face with four possible names (i.e., the correct name and three other names). The name associated with the face as learned during the encoding phase has to be chosen as quickly as possible. Scores range from 0 to 12, with higher scores meaning a better outcome.	Immediately before and after intervention
Secondary	Change in spectral source space resting-state MEG	Change in absolute and relative power will be used.	Immediately before and after intervention
Secondary	Change in functional connectivity source space resting-state MEG	Change in corrected amplitude envelope correlation (AEC-c) and phase lag index (PLI) will be used.	Immediately before and after intervention
Secondary	Change in source space resting-state MEG network structure	Change in graph theory parameters will be used as a measure of: Global network structure: Minimum spanning tree (MST) variables (e.g. leaf number, eccentricity, betweenness centrality); Clustering coefficient and path length; Mesoscale network structure: - Modularity measures; Nodal characteristics: (Weighted) degree; Eigenvector centrality	Immediately before and after intervention